PDBsum entry 32c2

Immune system

PDB id: 32c2

Contents

Protein chains

217 a.a. *

218 a.a. *

* Residue conservation analysis

PDB id:

32c2

Name:

Immune system

Title:

Structure of an activity suppressing fab fragment to cytochrome p450 aromatase

Structure:

Igg1 antibody 32c2. Chain: a. Fragment: light chain, variable region. Igg1 antibody 32c2. Chain: b. Fragment: heavy chain, variable region

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090

Biol. unit:

Dimer (from PQS)

Resolution:

3.00Å R-factor: 0.213 R-free: 0.317

Authors:

M.W.Sawicki,P.C.Ng,B.Burkhart,V.Pletnev,T.Higashiyama,Y.Osawa,D.Ghosh

Key ref:

M.W.Sawicki et al. (1999). Structure of an activity suppressing Fab fragment to cytochrome P450 aromatase: insights into the antibody-antigen interactions. Mol Immunol, 36, 423-432. PubMed id: 10449095 DOI: 10.1016/S0161-5890(99)00062-0

Date:

21-Apr-99 Release date: 26-Apr-00

Protein chain

No UniProt id for this chain

Struc: 217 a.a.

Protein chain

No UniProt id for this chain

Struc: 218 a.a.

DOI no: 10.1016/S0161-5890(99)00062-0

Mol Immunol 36:423-432 (1999)

PubMed id: 10449095

Structure of an activity suppressing Fab fragment to cytochrome P450 aromatase: insights into the antibody-antigen interactions.

M.W.Sawicki, P.C.Ng, B.M.Burkhart, V.Z.Pletnev, T.Higashiyama, Y.Osawa, D.Ghosh.

ABSTRACT

The crystal structure of a Fab fragment (Fab3-2C2) of a monoclonal antibody raised against aromatase cytochrome P450 P450arom) has been determined at 3.0 A resolution. P450arom is a membrane bound enzyme responsible for the catalysis of indrogens to estrogens, the process of aromatization, and hence has been implicated in hormone-dependent breast cancer. The Fab fragment of MAb3-2C2 IgG suppresses P450arom activity in a dose dependent manner. The Fab3-2C2 molecule crystallizes n the space group P2(1)2(1)2(1) with a unit cell of a= 154.89 A, b = 73.51 A, and c= 36.90 A. The crystal structure consists of a light and a heavy chain in the asymmetric unit, each characterized by the greek-key antiparallel beta barrel folding seen in all Fab structures. The average elbow angle between the two domains is 143 degrees. Modeling of the interactions between the variable domains of the antibody and a known model of P450arom maps the epitope to a region of the enzyme that is consistent with the available biochemical data and the activity-suppressing function of the antibody. The epitope mapping result is further supported by the inability of MAb3-2C2 IgG to suppress the activity of, or to interact with placental porcine P450arom, which is 81% identical (86% similar) to human P450arom but has a few key substitutions in the putative epitope region.